# ELD607 Orai1 Antagonist Increases Bacterial Clearance from the Lung

> **NIH NIH R42** · ELDEC PHARMACEUTICALS, INC. · 2020 · $300,000

## Abstract

Hospital acquired pneumonia (HAP) is most common cause of mortality in intensive care units and the 2nd most
common nosocomial infection in the US. P. aeruginosa, S. aureus (including MRSA) and other ESKAPE
pathogens are common causes of HAP. The rise in antibiotic-resistant bacteria, including MRSA, further
complicates the challenges of delivering effective treatments in this patient population. New approaches beyond
traditional antibiotics are urgently need to improve outcomes in HAP patients. The innate immune protein Short
Palate LUng and Nasal epithelial Clone 1 (SPLUNC1) is secreted into the lung lumen, where it can bind to and
regulate ion channels. Orai1 is a ubiquitously-expressed plasma membrane Ca2+ channel, whose activation is
required for the onset of inflammation. We have identified SPLUNC1’s Orai1-inhibitory domain, termed the a6
region: SPLUNC1 and a6 negatively regulate Orai1 to moderate Ca2+ signaling and reduce inflammation.
However, both SPLUNC1 and the a6 peptide are rapidly degraded by neutrophil elastase, limiting their
effectiveness in reducing Ca2+ signaling and inflammation in pneumonia, which is characterized by neutrophilia.
Eldec Pharma has developed a robust, novel peptidomimetic called ELD607, which reconstitutes
SPLUNC1/a6’s ability to inhibit Orai1, yet is significantly more resistant to degradation by neutrophil elastase
than a6. In murine pneumonia models with P. aeruginosa and S. aureus, a single, inhaled dose of ELD607
reduced lung neutrophilia by 90%, decreased lung bacterial infection by 3-5 log10 CFUs, reduced sepsis, and
increased survival. These definitive experiments demonstrate that rebalancing the lung’s inflammatory response
via ELD607 enhances the lungs’ natural ability to clear pathogens, in the absence of antibiotics. This capacity is
predicted to make concurrently-administered antibiotics more effective, providing an important new therapeutic
strategy to help address the emergence of antibiotic-resistant strains of bacteria. The ability of ELD607 to
inhibit Orai1 and increase bacterial clearance represents a revolutionary approach to improving HAP
outcomes. Robust validation of ELD607 in Phase I will enable Eldec Pharma to request a pre-IND meeting with
the FDA, in order to perform IND-enabling studies in Phase II and to make the subsequent transition to clinical
development.
Phase 1
Aim 1. To confirm that ELD607 replicates the Orai1-tropism observed with SPLUNC1/a6.
Aim 2. To replicate ELD607’s ability to clear other ESKAPE pathogens.
Phase 2
Aim 3 To produce GLP grade ELD607 to support downstream development activities.
Aim 4. To determine the optimal dosing regimen of ELD607 in a murine model.
Aim 5. To validate the ELD607 dosing regimen in a Rhesus macaque model of HAP.

## Key facts

- **NIH application ID:** 10080273
- **Project number:** 1R42AI155107-01
- **Recipient organization:** ELDEC PHARMACEUTICALS, INC.
- **Principal Investigator:** Robert Tarran
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2020-06-22 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080273

## Citation

> US National Institutes of Health, RePORTER application 10080273, ELD607 Orai1 Antagonist Increases Bacterial Clearance from the Lung (1R42AI155107-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10080273. Licensed CC0.

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